This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To explore the possibility that dietary restriction retards aging processes in a nonhuman primate species. This Program Project has provided a wealth of new information about the biology of aging and how the manipulation of diet can influence the process of growing old. PROGRESS: Monkeys eating 30 percent fewer calories of a nutritionally complete diet exhibit better health than study controls. Reduced caloric intake seems to slow basic aging processes and may extend the maximum life span in primates, as has been shown in rodents. Diabetes develops less frequently in monkeys on a restricted diet. Animals allowed to eat freely have a greater incidence of diabetic or pre-diabetic conditions. Fasting basal insulin and glucose concentrations are lower in monkeys on a restricted diet. Both fat mass and fat-free mass were lower in monkeys on a restricted diet. Monkeys on a reduced-calorie diet have fewer signs of spinal arthritis, a condition that manifests itself with age in both rhesus monkeys and humans. Fewer calories may reduce the risk of vascular disease. Caloric restriction altered circulating LDL in a manner that may inhibit atherogenesis. Caloric restriction retards several age- dependent physiological and biochemical changes in skeletal muscle, including oxidative damage. Controlled caloric restriction has not disrupted menstrual cycles of female monkeys. The next period of study should be even more insightful as the oldest monkeys in the study are now truly old. During this phase, age-related diseases and disorders appear more frequently, including adult-onset diabetes, osteoporosis, cancers, obesity, hypertension and the loss of skeletal muscle mass. This research used Animal Services, Assay Services and Pathology Services. PUBLICATIONS: Anderson RM, Colman RJ: Prospects and perspectives in primate aging research. Antiox. Redox Signal. 14(2):203-205, 2011. PMCID: PMC3000241, PMID: 20712396. Anderson RM, Weindruch R: Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol. Metab. 21(3):134-141, 2010. PMCID: PMC2831168, PMID: 20004110. Bendlin B, Canu E, Willette AA, Kastman EK, McLaren DG, Kosmatka KJ, Xu G, Field AS, Colman RJ, Coe CL, Weindruch R, Alexander AL, Johnson SC: Effects of aging and calorie restriction on white matter in rhesus macaques. Neurobiol Aging. 2010 Jun 10. [Epub ahead of print] PMCID: PMC2939965, PMID: 20541839 Colman RJ, Anderson R: Nonhuman primate calorie restriction. Antiox. Redox Signal. 14(2):229-239, 2011. PMCID: PMC3000242. PMID: 20698791. Fowler CG, Chiasson KB, Leslie TH, Thomas D, Beasley TM, Kemnitz JW, Weindruch R: Auditory function in rhesus monkeys: effects of aging and caloric restriction in the Wisconsin monkeys five years later. Hear. Res. 261(1-2):75-81, 2010. PMCID: PMC2855903, PMID:20079820. Kastman EK, Willette AA, Coe CL, Bendlin BB, Kosmatka KJ, McLaren DG, Xu G, Canu E, Field AS, Alexander AL, Voytko ML, Beasley TM, Colman RJ, Weindruch R, Johnson SC: A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys. J Neurosci. 30(23):7940-7947, 2010. PMCID: PMC2898557, PMID: 20534842. McKiernan SH, Colman RJ, Lopez M, Beasley TM, Aiken JM, Anderson RM, Weindruch R: Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle. Exp. Gerontol. 46(1):23-29, 2011. PMCID: PMC2998549, PMID: 20883771 Willette AA, Bendlin BB, McLaren DG, Canu E, Kastman EK, Kosmatka KJ, Xu G, Field AS, Alexander AL, Colman RJ, Weindruch RH, Coe CL, Johnson JC: Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys. Neuroimage. 51(3):987-994, 2010. PMID: 20298794, PMCID: PMC2877377. Willette AA, Gallagher C, Bendlin BB, McLaren DG, Kastman EK, Canu E, Kosmatka KJ, Field AS, Alexander AL, Colman RJ, Voytko ML, Weindruch RH, Coe CL, Johnson SC: Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys. Neurobiol Aging. 2010 Aug 4. [Epub ahead of print]. PMID: 20691506.